Deregulated Wnt/b-catenin signaling underlies the pathogenesis of a broad range of human cancers including multiple myeloma (MM). Thus, the b-catenin transcriptional complex has emerged as a high-priority pharmacologic target. The BCL9 oncogene is a critical transcriptional co-activator of b-catenin, and studies from our laboratory have implicated this transcriptional complex in MM disease initiation and progression. Micro RNAs regulate the expression of oncogenes and tumor suppressor genes, and because they play important roles as biologic inhibitors of cancer growth, they have great potential as novel therapeutic agents. Here we provide evidence for a role of miR-30s family in regulating expression of BCL9 and as a novel therapeutic agent in MM.